I hypothesize that in Caenorhabditis elegans there exists a signal from the nervous system to other nonneuronal cell types to globally control aging throughout the whole animal. I propose that disruption of this signaling pathway from the neurons to the target tissues, as well as disruption of the response pathway to that signal within the downstream cell types, will potently affect aging in C. elegans. The results from this proposal will identify and assemble the players of this signaling pathway through the use of both classical genetics and RNAi methodologies. Because cellular triggers, such as reactive oxygen species (ROS) have been shown to influence aging, apoptosis, and cellular senescence, this proposal will ultimately provide fundamental knowledge about the mechanisms that regulate longevity and cancer at the molecular level. Furthermore, because many cellular responses are highly conserved between nematodes and mammals, a detailed characterization of these pathways in C. elegans will lead to a more complete understanding of these specific cellular fates in humans.